Kelvin Kwan, PhD, Instructor in Neurobiology at Harvard Medical School, Boston, has been investigating ways to create large amounts of hair cells needed for research and cell-based therapies.
One of the challenges in hair cell research is the difficulty in harvesting enough hair cells to perform molecular experiments. An inner ear may have only 10-30,000 hair cells, so thousands of animals – typically mice, which are also very expensive to maintain – may be needed to collect enough hair cells for experiments. Additionally, inner ears are tiny and very hard to dissect in order to get at the various tissues. “This is a huge impediment in hair cell research,” Kwan says. He hopes to develop techniques to create hair cell lines that will continuously divide and have the potential to differentiate into functional human hair cells.
In order to generate a cell line, Kwan introduced transcription factors, molecules that bind to DNA and work at the genetic level, into progenitor cells. These transcription factors “reprogram” cells by remodeling chromatin and influence gene expression. Progenitor cells are similar to stem cells, in that they continually divide; however, they are “lineage restricted” and can only become a few kinds of inner ear cells, including hair cells. Because of their restriction, not only are they easier to guide down the path to become hair cells, more hair cells can be made. The ability to generate large numbers of a specific cell type overcomes a major hurdle for cell-based therapies. So far, his techniques are promising to yield more hair cells than any other method.
In addition to promoting cell based therapies, progenitor cells can be used for discovering drugs to treat deafness. “If you could find a specific compound that turns a progenitor cell into a hair cell, you could isolate that compound and possibly regenerate hair cells in deaf animals.” While this is the long term goal of Kwan’s research, for now, he is interested in perfecting his process for growing large numbers of hair cells for experimentation.